The applicants will develop radiopharmaceuticals to target Folate Binding Protein (FBP) which is a receptor that is overexpressed on a wide variety of tumor cells. Previous data have shown that folic acid (folate; a vitamin) as well as macromolecules conjugated to folate, bind to this receptor and are taken into the cell by receptor-mediated endocytosis. Folate will be conjugated to chelating agents to allow labeling with radioisotopes of Ga, In, Cu, Tc and/or Re. Initially, conjugates containing macroscopic amounts of the nonradioactive metals will be prepared for physicochemical characterization. Radiolabeled folate conjugates will be tested for their affinity in vitro for tumor cells of the MDA-231 breast cancer cell line and the KB nasopharyngeal cancer cell line, both of which exhibit FBP. The A-549 lung cancer cell line which does not display FBP will be used as a receptor-negative control. Human tumors from the same cell lines will be grown in nude mice for in vivo testing of the tumor uptake of the most promising radiolabeled folate conjugates. Competitive binding studies with unlabeled folate will be performed to demonstrate that radiotracer localization in tumor is a saturable receptor-dependent process. A second animal model (dogs with spontaneous neoplasms) will be used to further evaluate the ability of the most promising radiolabeled conjugates to image tumor over background.